Transplantation Without Overimmunosuppression (TWO) study protocol: A phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients

Matthew Oliver Brook*, Joanna Hester, William Petchey, Ines Rombach, Susan Dutton, Matthew James Bottomley, Joanna Black, Seetha Abdul-Wahab, Andrew Bushell, Giovanna Lombardi, Kathryn Wood, Peter Friend, Paul Harden, Fadi Issa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Introduction Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy. Methods and analysis 60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications. Ethics and dissemination Ethical approval has been provided by the National Health Service Health Research Authority South Central - Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. Trial registration number ISRCTN: 11038572; Pre-results.

Original languageEnglish
Article numbere061864
JournalBMJ Open
Volume12
Issue number4
DOIs
Publication statusPublished - 15 Apr 2022

Keywords

  • Clinical trials
  • IMMUNOLOGY
  • Nephrology
  • TRANSPLANT MEDICINE
  • Transplant surgery

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